Acquired immune deficiency syndrome (AIDS) is a life-threatening disease caused by the human immunodeficiency virus (HIV). Two strains of HIV have been recognized: HIV-1 is responsible for most cases of AIDS, whereas HIV-2 is increasingly being found in West Africa. AIDS was first reported in 1981 in the United States and it is estimated that over one million people in the United States are now infected with HIV. Evidence suggests that almost everyone infected will develop symptoms within 10 years and that they will eventually develop the disease if they do not die of some other cause. The few cases of HIV-infected individuals who have not developed AIDS, even after many years of being infected, are a being investigated.

HIV is transmitted from an infected to a noninfected person in body fluids such as blood, semen, or vaginal secretions. The major methods of transmission are intimate sexual contact, contaminated needles used by intravenous drug users, and blood products. Present evidence indicates that household, school, or work contacts do not result in transmission.

In the United States, most cases of AIDS appear in homosexual or bisexual men and in intravenous drug users. A small percentage of cases have resulted from transfusions or contaminated clotting factors used by hemophiliacs. Sadly, children can be infected before birth, during delivery, or after birth from breast feeding. A few cases of AIDS have occurred in health care workers accidentally exposed to HIV-infected blood or body fluids, and an even fewer number of cases of health care workers infecting patients has been documented. The most rapidly increasing group of AIDS patients in United States is herosexual males or females who have had sexual contact with an infected person. Women in the 15-to-25-year-old age group appear to be especially likely to contract AIDS, possibly because the vaginal mucous membranes of women in this age group are thin and are a less effective barrier to the virus.

In other countries the pattern of AIDS cases can be different from that in the United States. For example, in Haiti and central Africa, heterosexual transmission is the major route of spread of HIV. Worldwide, about 40% of AIDS cases are females. It is estimated that by the year 2000 there will have been 40 million cases of AIDS.

Preventing transmission of the HIV is presently the only way to prevent AIDS. The risk of transmission can be reduced by educating the public about safe sexual practices such as reducing one's number of sexual partners, avoiding anal intercourse, and using a condom. Public education also includes warnings to intravenous drug users of the dangers of using contaminated needles. Ensuring the safety of the blood supply is another important preventive measure. In April l985, a test for HIV antibodies in blood became available. Heat treatment of clotting factors taken from blood has also been effective in preventing transmission of HIV to hemophiliacs.

HIV infection begins when a viral protein called gp120 binds to a surface molecule of cells known as CD4. The CD4 molecule is found primarily on helper T cells, and it normally enables helper T cells to adhere to other lymphocytes, for example, during the process of antigen presentation. Certain monocytes, macrophages, neurons, and neuroglial cells also have CD4 molecules. Once attached to the CD4 molecules, the virus injects its genetic material (RNA) and enzymes into the cell. The viral RNA and enzymes produce DNA that can direct the formation of new HIV RNA and proteins; that is, additional viruses that can infect other cells.

The manifestations of AIDS can virtually all be explained by the loss of helper T cell functions or the infection of other cells with CD4 molecules. Without helper T cells, cytotoxic T and B cell activation is impaired, and specific resistance is suppressed. At first, it was thought that cell death resulted directly from the effects of the virus. It is now believed that the process is more complicated, involving immune system responses. Possibilities include cytotoxic T cells attacking infected helper T cells, antibodies interfering with antigen presentation by attaching to gp 120 and MHC antigens, and anergy. Anergy of helper T cells could occur if co-stimulation is prevented by gp 120 that becomes detached from HIV and binds to CD4 molecules, preventing them from functioning. These and other possibilities are currently being investigated.

Following infection by HIV, within 3 weeks to 3 months some patients develop an acute (sudden) mononucleosis-like syndrome that can last up to 14 days. Symptoms include fever, sweats, fatigue, muscle and joint aches, headache, sore throat, diarrhea, rash, and lymphadenopathy (swollen lymph nodes). More commonly there is a persistent version of the syndrome that lasts for several months and includes lymphadenopathy, fever, and fatigue. This condition has been called AIDS-related complex (ARC). During this time the patient becomes positive for HIV antibodies, and within a year many patients develop AIDS.

The most common clinical manifestations of AIDS include testing positive for HIV antibodies, a decrease in helper T cell numbers to less than 200/mm3 of blood, the presence of opportunistic infections such as tuberculosis or recurrent pneumonia, and Kaposi's sarcoma or invasive cervical carcinoma. Normally there are about 1200 helper T cells/mm3 blood, but between the time of infection and the development of AIDS the number or helper T cells decreases. Apparently most HIV replication takes place in the lymph nodes, where helper T cells and other immune cells aggregate. As cells in the lymph nodes are destroyed, the number of circulating helper T cells decreases.

Opportunistic infections involve organisms that normally do not cause disease, but can do so when the immune system is depressed. Examples include Pneumocystis carinii pneumonia (caused by an intracellular protozoan); tuberculosis (caused by intracellular bacteria); syphilis (caused by sexually transmitted bacteria); candidiasis (a yeast infection of the mouth or vagina); and protozoans that cause severe, persistent diarrhea. Kaposi's sarcoma is a type of cancer that produces lesions in the skin, lymph nodes, and visceral organs. Also associated with AIDS are symptoms resulting from the effects of HIV on the nervous system, including motor retardation, behavioral changes, progressive dementia, and possibly psychosis.

There currently is no cure for AIDS. Management of AIDs can be divided into two categories: (1) management of secondary infections or malignancies associated with AIDS, and (2) treatment of the HIV infection itself. Management of secondary infections uses three approaches: prevention of infection, treatment of active infection, and prevention of recurrence of infection. Drugs such as pentamidine, sulfamethoxazole, and trimethoprim have proven effective against P.carinii, and specific treatments are available for many other secondary infections or malignancies.

Azidothymidine (also known as AZT or zidovudine) inhibits the replication of HIV by preventing HIV ribonucleic acid from producing deoxyribonucleic acid inside cells. AZT can delay the onset of AIDS but does not appear to increase the survival time of AIDS patients. However, the number of babies who contract AIDS from their HIV-infected mothers can be dramatically reduced by giving AZT to the mothers during pregnancy and to the babies following birth. AZT can produce serious side effects such as anemia or even total bone marrow failure. Resistance to AZT often develops after 6 to 18 months of treatment, and there is clearly a need for alternative treatments. Another drug, dideoxyinosine (ddl), which also prevents HIV replication, has proven to be effective. A combination approach using AZT, ddl, and pyridinone has prevented HIV replication in the test tube. Multiple drugs may be necessary to treat AIDS. Although HIV can mutate and become resistant to any one drug, it is unlikely that HIV can become resistant to several drugs at the same time.

A different approach uses CD4 molecules produced through genetic engineering as 'decoys". Infection of cells may be prevented if the HIV binds to these "decoys" instead of the CD4 molecules of cells. The results of this therapy have been disappointing.

The ultimate goal is to produce a vaccine that prevents AIDS, and many different strategies are under development. Simian immunodeficiency virus (SIV) causes a type of AIDS in monkeys. A vaccine using live but disabled SIV produced a low-level infection that caused no illness but induced an immune response in rhesus monkeys. Such a vaccine might work in humans, but there is considerable danger in using live HIV because it is always possible that not all of the viruses in a vaccine have been killed. Another approach is to use a part of the virus that could not cause an infection, for example, peptides derived from proteins of the outer viral coat. An advantage of this approach is that peptides from different stains of HIV could be used in a single vaccine. Clinical trials of this type of vaccine are underway.

Although antibody production may prevent infection, another strategy is to stimulate cell-mediated immunity to kill any cells that are infected. By removing the sites of HIV replication, infections could be prevented and possibly cured. A vaccine using the enzymes infected by the HIV into cells may stimulate such cell-mediated response. Hopefully, an effective vaccine using these or other strategies will be come available.

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